tbuckley/cabot-search huggingface dataset:
Abstract 19136: Barriers to Equitable Access to Acute Stroke Care in Hawaii: Logistical and Socioeconomic Effects on Stroke Care in an Island Chain
Authors: Trevor H Torigoe, Taysia Morioka, Melissa Kahili-Heede, Ferdinand Hui, Matthew Koenig, Kazuma Nakagawa
Journal: Circulation (2023)

Introduction: Stroke is the leading cause of chronic disability and third-leading cause of mortality in Hawaii. State incidence of stroke is lower (2.9% to 3.4%) but mortality is higher (70.3:100,000) compared to the rest of the country (58.1:100,000). Access to comprehensive acute stroke care is complicated by geographical restrictions including topography and isolation between islands and also socioeconomic factors such as cost of living. The Queen’s Medical Center (QMC, Honolulu, Oahu, HI) is the sole comprehensive stroke center in the state. Hypothesis: Access to comprehensive stroke care and thrombectomies will be negatively correlated with both travel time and increased geographical barriers. Methods: Retrospective review of records from QMC between January 2021 to June 2023 identified 405 patients with an acute stroke and underwent thrombectomy. Patient zip codes were used to create a heat map identifying locations of patients receiving thrombectomy. Another heat map was made for all acute stroke cases using public health data. An index was created to determine travel time from zip code to QMC. Thrombectomy and acute stroke versus travel time was performed using generalized linear models. Results: GIS-generated heat maps demonstrate a difference in care opportunities between zip codes, identifying areas with highest incidence of acute stroke associate with lower rates of thrombectomy procedures. Island barriers create the highest differences in acute stroke cases versus thrombectomy procedure. Regression analysis demonstrated marked negative correlation in comparison between thrombectomies versus acute stroke cases with respect to travel time. Conclusions: Healthcare providers in Hawaii face an increased challenge with respect to providing care due to natural geography that extending the time to comprehensive stroke treatment. Hawaii is acutely aware of the unique challenges and the results of this study are an initial phase in providing a framework for modified statewide acute stroke protocols that can further be utilized by other communities with similar barriers to access to care.
Abstract 16929: Defining Thresholds for Meaningful 30-day Health Status Changes Following Transfemoral Carotid Artery Stenting
Authors: Jonathan Kluger, Gaelle Romain, Jacob Cleman, Lindsey Scierka, Scott Grubman, Carmen S Pajarillo, Christopher Schenck, Carlos Mena-Hurtado, Kim G Smolderen
Journal: Circulation (2023)

Introduction: Carotid artery stenosis treatment trials have focused on clinical endpoints such as stroke, death, and MI, but evidence of carotid revascularization’s impact on health status is limited. This study aims to establish minimal clinically important differences (MCIDs) to assess clinical improvement or worsening from the perspectives of patients with carotid artery stenosis undergoing transfemoral carotid artery stenting (TF-CAS). Methods: We studied patients in the multicenter Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) registry who underwent TF-CAS between 2010 and 2014 and who completed either the EQ-5D-3L or SF-36, two generic health-related quality-of-life surveys. Distribution-based MCIDs were calculated as 0.5 standard deviations for 30-day changes in health status scores post-TF-CAS for the EQ-5D-3L index value and visual analog scale (VAS) subscales and the SF-36 mental and physical component summary (MCS and PCS) subscales. We then stratified this analysis by symptom status (presence or abscence of prior stroke or TIA). Results: The study included 3,930 patients (27.7% symptomatic) who completed the EQ-5D-3L and 3,018 (30.5% symptomatic) who completed the SF-36. The MCIDs for the overall cohorts were 0.09, 11.02, 4.73, and 5.39 for the EQ-5D-3L index value, EQ-5D-3L VAS, SF-36 MCS, and SF-36 PCS, respectively. All MCIDs are summarized in Table 1. The MCIDs for each subscale were similar between asymptomatic and symptomatic subpopulations. Conclusions: Distribution-based thresholds for improvement and worsening of health status in patients undergoing TF-CAS were established for commonly-used generic health status instruments. These reference values can be used in both symptomatic and asymptomatic disease and will be important for interpreting future trial results focusing on the benefit of TF-CAS from patients’ perspectives.
Abstract 16092: Oncology Meets Cardiology: Sustained Ventricular Tachycardia With a Pulse
Authors: Palwinder Sodhi, Steven Ewer
Journal: Circulation (2023)

Introduction: Palpitations are one of the most common presenting symptoms. While usually benign, they can be life-threatening. We present a case of a sustained VT in the setting of a rare transformation of Follicular Lymphoma (FL). Case Description: An 86-year-old female with a history of FL with cardiac involvement, hypothyroidism, and hypertension presented with three episodes of palpitations. The first lasted about 20 minutes and spontaneously resolved. The second occurred a few hours later and was resolved within 15 minutes. Her third did not resolve. On presentation, she was complaining of palpitations and lightheadedness. BP 136/97, HR 193. Physical exam revealed no respiratory distress, rapid rate, clear lung fields, and unremarkable neurological exam with clear mentation. ECG (below) demonstrated sustained VT with rates of ~260 bpm. Amiodarone bolus was started. Cardioversion was attempted, but her VT degenerated into Ventricular Fibrillation. She achieved ROSC and was admitted with sinus rhythm. It was suspected that her FL had transformed into a more aggressive lymphoma, i.e. Diffuse Large B cell Lymphoma (DLBCL). On Cardiac MRI, she had metastasis to the right AV groove consistent with cardiac lymphoma, which was the etiology of her arrhythmia. She elected to enroll in hospice and was discharged in sinus rhythm. Impact/Discussion: Histological transformation (HT) of indolent non-Hodgkin lymphoma subtypes (FL) to clinically aggressive subtypes (DLBCL) is estimated to occur 1-2 %/year. Although there have been studies examining risk factors suggestive of HT, much still needs to be studied to effectively manage patients with cardiac metastasis. In this case, metastasis involved the right AV groove, which was the cause of her arrhythmia. Patients with sustained VT usually present with severe symptoms including cardiac arrest, but can present with mild symptoms, as was the case of this patient. Prompt evaluation and management of palpitations is paramount.
Abstract 13873: Deep Learning-Based GWAS of Aortic Valve Function Links 81 Loci to Aortic Stenosis Risk
Authors: James Pirruccello, Shinwan Kany, Joel Ramo, Cody Hou, Sean J Jurgens, Victor Nauffal, Jonathan Cunningham, Emily Lau, Jennifer E Ho, Jeff Olgin, Sammy Elmariah, Mark E Lindsay, Aarno Palotie, Patrick T Ellinor
Journal: Circulation (2023)

Background &amp; Aims: The genetic influences on normal aortic valve (AV) function and their impact on aortic stenosis (AS) risk are of significant interest. We sought to identify common genetic determinants of normal variation in AV function, and to understand their relationship with clinical disease. Methods: We used deep learning to measure peak velocity, mean gradient, and aortic valve area from MRI in UK Biobank participants. We conducted genome-wide association studies (GWAS) in a subset of 44,780 participants without cardiovascular disease. We performed multi-trait analysis of GWAS (MTAG) to incorporate data from AV measurements and AS diagnoses in UK Biobank and FinnGen, and applied PRScs to construct polygenic scores (PGS). Results: In the unadjusted analysis, 26 loci were associated with at least one AV measurement. Incorporating the AS GWAS using MTAG, we identified 81 distinct loci (62 with AV traits, 54 with AS, 35 overlapping), including PCSK9 (β=0.032, P=5.8E-09) and LDLR (β=0.018, P=2.3E-10). Additional loci were associated with lipid metabolism (LPA, FADS2, SORT1), atherosclerosis (CDKN2B, ARHGEF26, OTUD7B, PRDM16), inflammation (IL6, KLF2, TRAF1), and cardiac development and aortic root function (SMAD3, GATA4, ELN, TBX20, TEX41). The PGS for the unadjusted mean gradient was predictive of AS in FinnGen (HR 1.36 for the top 5% of participants vs all others, P=1.8E-14). All of Us participants in the top 5% of the MTAG-adjusted peak velocity PGS had an HR of 2.5 for incident AS (P=4.4E-08). Mendelian randomization showed association between Lp(a) and LDL—but not ApoA—on greater peak velocity (P=2.7E-13, P=1.6E-16, and P=0.60, respectively). Conclusion: We identified 81 genetic loci linked to AV function or AS. AV measurement PGS were strong predictors of AS risk. ApoB and Lp(a) showed causal association with higher peak velocity. These findings have implications for the early pathogenesis of AS and suggest modifiable pathways as targets for prevention.
Abstract 16081: Cardiovascular Outcomes of Individuals With Sleep Deprivation; a Retrospective Population-Based Analysis
Authors: Endurance O Evbayekha, Carlos Gaibor, Yara Jelwan, Purav Desai, Rani Kuttab, Leonela Bastidas, Amer Abbas, Brittany Dixon, Shane LaRue
Journal: Circulation (2023)

Introduction: Inadequate sleep quality and duration have been linked to adverse cardiovascular effects. Examining the cardiovascular outcome profile of the inpatient population with sleep deprivation (SD) has been relatively scarce. We aimed to study the outcomes in this setting. Hypothesis: We hypothesize that SD is associated with adverse cardiovascular outcomes, and studying the effect will help inform clinical care and prevention strategies. Methods: We used the ICD-10 code to identify all hospitalizations aged 18-85 with a primary or secondary SD diagnosis from the Nationwide Inpatient Database (NIS) 2016-2020. We excluded individuals with sleep apnea and those with established SD due to medical or psychiatric illnesses. A multivariate logistic regression model was used to account for confounders (including demography, smoking history, hospital setting, and insurance type) and estimate the probability of outcomes. Our outcomes of interest were hypertension (HTN), dyslipidemia (DysL), and obesity. Results: There were 27,294,891 hospitalizations aged 18-85 during the study period, and 2.6% (718,083) had a sleep deprivation diagnosis, mean age of 57.7 years ± 17. Of these, 74.8% (519497) were Caucasians, 12.1% (84463) were Blacks, and 8.1% (56316) were Hispanics. Individuals with SD had a higher likelihood of HTN, adjusted odds ratio (aOR) =1.28 (1.27-1.30, p&lt;0.0001), DysL 1.3 (1.2-1.3, p&lt;0.0001), and obesity 1.02 (1.01-1.02, p&lt;0.0001). Conclusions: Our analysis showed that sleep deprivation was associated with a higher likelihood of hypertension, dyslipidemia, and obesity. Encouraging lifestyle modification, including adequate sleep hygiene, cannot be overstated.
Abstract 19123: Associations Between Multiple Dimensions of Poor Sleep and Life’s Essential 8 Cardiovascular Health Score During the Menopausal Transition: Findings From the AHA Research Goes Red Weight Study
Authors: Brooke A Aggarwal, Samantha Scaccia, Gary Charliyan, Pengchen Wang, Matthew A Allison, Janet M Catov, Harmony Reynolds, Dhananjay Vaidya
Journal: Circulation (2023)

Introduction: The sleep health metric in AHA Life’s Essential 8 (LE8), a measurement of cardiovascular health (CVH), consists only of sleep duration. Associations of other dimensions of sleep health including sleep quality with the LE8 CVH and its individual components have not yet been evaluated. Methods: Participants were 291 women (n=98 pre-, n=94 peri-, n=99 post-menopausal, mean age=50 ± 3.2yr) between 45-55y from the AHA Research Goes Red Weight Study, which utilized Verily’s online platform. Standardized questionnaires included the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Berlin questionnaire for risk of obstructive sleep apnea (OSA), and a 1-wk NIH ASA 24-Hour Dietary Assessment. The LE8 CVH and component scores were computed. Cross-sectional associations between sleep and overall CVH scores and individual metrics were tested using multivariable logistic regression models adjusted for age, race/ethnicity, education, employment, insurance, and menopausal status. Results: Half of women slept &lt;7 hours/night, 79% reported poor sleep quality (PSQI≥5), one-third had high-risk OSA phenotype, 51% reported insomnia symptoms (ISI≥8), and 12% had evening chronotype. Compared to pre-menopausal women (67%), significantly more post-(83%) and peri-menopausal (86%) women reported poor sleep quality (p&lt;0.01). Women with poor sleep quality had 3-fold higher odds of poor overall CVH score (p=.04). Women with high-risk OSA phenotype and evening chronotype also had ~3-fold higher risk of poor overall CVH scores (OR=3.58, CI=1.79-7.18, and OR=3.33, CI=1.45-7.69, respectively). Poor sleep quality was associated with greater odds of low score on the diet component (OR=2.97, CI=1.55-5.69). Insomnia symptoms were associated with poor score on the BMI component (OR=1.92, CI=1.15-3.21). High-risk OSA phenotype was associated with greater odds of poor scores on the blood pressure, blood glucose, and BMI components (OR=2.3, CI=1.2-4.3; OR=3.2, CI=1.5-7.1, and OR=11.6, CI=6.2-21.6). Conclusions: Multiple aspects of sleep other than duration were associated with overall LE8 CVH score, and individual metrics, among women across menopause. Findings support potential incorporation of sleep quality into CVH constructs.
Abstract 15612: EDG-7500, a Novel Cardiac Sarcomere Regulator That Preserves Intrinsic Myosin-Motor Function, Improves Cardiac Function and Reserve in a Minipig Model of Hypertrophic Cardiomyopathy
Authors: Carlos L Del Rio, Cassady Rupert, Jessica Tolley, Mike Duvall, Craig Emter, Emy DiNatale, Natalie Hawryluk, ALAN RUSSELL, marc Semigran, Marc Evanchik
Journal: Circulation (2023)

Introduction: Hypertrophic Cardiomyopathy (HCM) is a myocardial disease characterized by LV hypertrophy, hyperdynamic contraction, and diastolic dysfunction that results in impaired exercise capacity. In HCM, excess acto-myosin crossbridge formation during diastole increases myocardial stiffness leading to hindered ventricular filling and limited cardiac reserve. EDG-7500, a novel sarcomere regulator that slows the rate of contraction but does not directly inhibit the myosin motor head, may offer salutary effects in HCM with minimal reduction in systolic performance. Here, this hypothesis was tested in the setting of the pathological HCM beta-myosin heavy chain (MYH7) R403Q mutation. Methods: In vitro, force dynamics were evaluated in human IPSC-derived engineered heart tissues (EHT) with the MYH7 R403Q mutation compared to isogenic controls (WT). The biomechanical effects of EDG-7500 were evaluated in permeabilized fibers from tissues isolated from minipigs carrying the MYH7 R403Q mutation. The in vivo cardiac responses to EDG-7500 were studied via echocardiography and invasive hemodynamics in the R403Q minipigs. In a subset of pigs, β-adrenergic receptor (β-AR) dependent cardiac output reserve was studied. Results: R403Q mutant EHT preserved peak force (PF) relative to WT but impaired relaxation kinetics (RT90: +19±4 ms, 171±4 vs. 152±2 ms in WT, P&lt;0.05). EDG-7500 (0.3uM) accelerated relaxation kinetics in R403Q EHTs (RT90: -8±3ms, 180±4 to 172±2 ms, P&lt;0.05) without affecting PF. RT90 improvement occurred at 6-fold lower concentrations than systolic inhibition (PF IC20: 1.95 ± 0.70 μM). In vivo, EDG-7500 improved early LV filling, accelerating e’ (6.9 ± 0.8 to 8.6 ± 0.6 cm/s, P &lt; 0.05) and decreased atrial volume (-22%, P &lt; 0.05) while enhancing β-AR dependent cardiac output recruitment; in R403Q pigs, EDG-7500 plus dobutamine led to higher cardiac outputs relative to only dobutamine (3.1±0.3 vs. 2.6±0.3 L/min, P&lt;0.05). Conclusions: EDG-7500, a novel cardiac sarcomere regulator, improved diastolic function in EHT and animals with the HCM-pathogenic MYH7 R403Q mutation, improving β-AR dependent cardiac output reserve. This novel profile could be valuable for the treatment of patients with HCM and diseases of diastolic dysfunction.
Abstract 13825: Post-PCI Outcomes in Patients on SGLT2 Inhibitor Therapy
Authors: Vishal R Dhulipala, Matthew Siano, Birgit Vogel, Serdar Farhan, Manish Vinayak, Anoop N Koshy, Ayush Arora, Kenneth Smith, Richard Tanner, Samantha Sartori, Samin K Sharma, Annapoorna Kini, Roxana Mehran
Journal: Circulation (2023)

Introduction: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to improve cardiorenal outcomes among patients with and without diabetes mellitus. Hypothesis: We aimed to investigate their impact on the risk of acute kidney injury (AKI) and major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI). Methods: Consecutive patients undergoing PCI at a high-volume PCI center between 2015 and 2022 were analyzed. Patients on SGLT2 inhibitors prior to PCI were compared to those not on SGLT2 inhibitors. The primary outcome was AKI, as defined as serum creatinine increase of ≥0.5 mg/dL or ≥25% from baseline within 30 days of PCI. MACE was defined as death or myocardial infarction (MI) and was assessed at 1 year post PCI. Results: There were significant differences in baseline clinical characteristics between patients on (n = 347) vs. not on (n = 16,594) SGLT2 inhibitors. Patients on SGLT2 inhibitors had higher prevalence of diabetes (90.5% vs. 45.5%), hypertension (96.8% vs. 92.1%), hyperlipidemia (95.7% vs. 90.5%), and prior CABG (21.0% vs 15.8%). SGLT2 inhibitor use was associated with a decreased rate of post-PCI AKI (3.3% vs. 6.6%; adjusted odds ratio [OR] 0.33; 95% confidence interval [CI] 0.08-0.89, P=0.025). At one year after PCI, patients on SGLT2 inhibitors had increased rates of MACE (8.2% vs. 3.9%; adjusted hazard ratio [HR] 1.74, 95% CI 0.99-3.06, P=0.052), driven by an increased risk of MI (6.9% vs. 2.1%; HR 2.63, 95% CI 1.42-4.90, P=0.002). Conclusions: SGLT2 inhibitor use was associated with lower post-PCI AKI, but was associated with an increased risk of MACE. The latter finding was driven by increased risk of MI, which may be explained by unmeasured confounders in these heterogeneous groups of patients.
Abstract 12525: Acute Pulmonary Edema, Mid-Ventricular Stress Cardiomyopathy and Cardiogenic Shock Following Intranasal Lidocaine/Epinephrine Administration During Septorhinoplasty
Authors: Andrii Maryniak, Filip Oleszak, Lucas Anderson, Adam Stys, Tom P Stys
Journal: Circulation (2023)

Case Presentation: A 19-year-old female presented for elective septorhinoplasty for nasal septal deviation and turbinate hypertrophy. After induction of anesthesia, and orotracheal intubation, pledgets soaked in 4% topical lidocaine with 1:1,000 epinephrine were placed in bilateral nares. Next, 1% lidocaine with 1:100,000 epinephrine was locally injected in the nasal mucosa to obtain hemostasis and analgesia. This resulted in transient hypertensive emergency, followed by undifferentiated shock requiring the initiation of norepinephrine. No signs of ischemia were seen on EKG. Chest X-ray revealed acute pulmonary edema. TTE showed reduced left ventricular systolic function, EF 30%, with mid-segment akinesis, consistent with mid-ventricular stress cardiomyopathy. Coronary angiography identified normal anatomy and patent arteries, supporting the diagnosis. Surveillance TTE after extubation and empiric treatment with metoprolol and losartan, showed improvement of EF to 45-50% and resolution of regional wall motion abnormalities. Discussion: Stress cardiomyopathy, also known as Takotsubo (TCM), is a rare form of cardiomyopathy accounting for 2-3% of ACS. The syndrome mainly affects the LV, causing a regional, transient, systolic dysfunction visualized on TTE or left ventriculography, that occurs in the absence of obstructive epicardial coronary lesions. Pathogenesis is poorly understood. Postulated mechanisms include catecholamine excess, coronary artery spasm and microvascular dysfunction. A systematic review found elevated norepinephrine levels in 74.3% of patients diagnosed with TCM, as was the case for our patient. Rapid systemic absorption of epinephrine can cause diffuse microvascular spasm and myocardial stunning. Catecholamine surge may also afflict direct myocardial toxicity, leading to disorganized cytoskeletal structures, excess extracellular matrix proteins and dysfunctional contractile properties of the myocardium.
Abstract 19166: Activity Level and Causes of Sudden Death: From the San Francisco Postmortem Systematic Investigation of Sudden Cardiac Death (POST SCD) Study
Authors: Brielle Kinkead, David Eik, Matthew Yee, Marwan M Refaat, Orrin Devinsky, Kosuke Nakasuka, Andrew Connolly, Ellen Moffatt, Zian H Tseng
Journal: Circulation (2023)

Introduction: Level of activity has a reported association with sudden death, but cardiac causes are presumed by convention. We investigated association between activity level and causes of presumed SCD (pSCD) in the San Francisco POstmortem Systematic InvesTigation of Sudden Cardiac Death (POST SCD) Study. Methods: POST SCD is a prospective cohort study using autopsy, clinical records, and toxicology to adjudicate arrhythmic (potentially rescuable with implantable defibrillator) or non-arrhythmic (e.g., tamponade, overdose) causes among pSCDs (WHO defined) 18-90 years in San Francisco. We included all incident cases from 2/1/11-3/1/14 (n=525) and incident cases approximately every 3rd day from 3/1/14-12/31/21 (n=358). Activity level at time of pSCD was determined by forensic investigator reports. For unwitnessed deaths, activity level was inferred based on time of arrest and location found. Activity level was classified as: sleep, recently awoke (&amp;lt10 min before death), awake with no activity (e.g., sitting), mild/moderate (e.g., bathing, feeding, walking), and rigorous (e.g., strenuous activity, sexual activity). Results: Of the total 883 pSCDs (mean 60 years, 73% male), 247 (28%) were sleeping, and 516 (58%) were awake at time of event. Cases with unclear circumstances (n=120, 14%) were excluded from analysis. Sleep was associated with non-cardiac cause of death (p=.01), specifically SUDEP (p=.02) and occult overdose (p&amp;lt.001). Wakefulness was associated with SAD (p=0.005), pulmonary embolism (p=.007), and vascular damage (p=.004) (Table). Nearly all cases engaging in rigorous activity at time of death (n=32) were SADs (31/32, 97%) and male (29/32, 91%). Conclusions: Most sudden deaths in this 11-year countywide postmortem study occurred during wakefulness. Sleep was associated with non-arrhythmic cause (specifically SUDEP and occult overdose), while wakefulness and rigorous activity were associated with arrhythmic cause of sudden death.